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G Isshiki

Publications and source records attributed to G Isshiki.

At least 55 records · Page 3Linked to original sources
PubMed1995

Newborn mass screening and molecular genetics of phenylketonuria in east Asia.

Phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH), and is performed with newborn mass screening. PKU causes irreversible mental retardation that can be prevented by a strict low-phenylalanine diet. More than 100 different mutations have been identified world wide and it has been revealed that PKU is a highly heterogeneous disorder. Here, we describe the progress of the molecular genetics of PKU in East Asia. Approximately 60% of all PKU alleles in East Asians have been characterized with 10 PKU mutations. Two major PKU mutations, R413P and IVS4nt-1, may have originated in different populations, spreading in prehistoric times through the Asian continent due to the founder effect, genetic drift, and bottleneck effect. We found different mutations in Caucasians and East Asians, thus PKU mutations have occurred after ethnic divergence between Caucasians and East Asians. Furthermore, PKU genotype and in vitro PAH activity in expression analysis correlates to the clinical and biochemical phenotypes in East Asians. The molecular defects at the PAH gene regulate the in vivo PAH activities and clinical manifestations.

Alleles↗
PubMed1995

[Oxalic acid].

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Adult↗
PubMed1995

[Citric acid].

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Adolescent↗
PubMed1993

The major mutation among Japanese patients with infantile Tay-Sachs disease: a G-to-T transversion at the acceptor site of intron 5 of the beta-hexosaminidase alpha gene.

A G-to-T substitution at the 3'-splice site of intron 5 in the beta-hexosaminidase alpha-subunit gene has been identified among Japanese patients with infantile Tay-Sachs disease. Of the 24 patients from 24 unrelated families, 15 were homozygous and 8 were heterozygous for this mutation (38/48 mutant alleles). The mutation causes a splicing abnormality, and the resultant mRNA lacks the exon 6 sequence. Northern blot analysis showed a single band of mRNA, distinctly shorter in size and slightly smaller in quantity than normal. Since exon 6 consists of 102 nucleotides, the mRNA should generate a beta-hexosaminidase alpha-subunit missing 34 amino acids in the middle but otherwise normal in the primary structure. It must be catalytically inactive or unstable, or both. The high frequency of this mutation among the Japanese patients with the infantile form of Tay-Sachs disease and its apparent absence outside of Japan suggests that this mutation may have originated in Japan.

Base Sequence↗
PubMed1993

Vertical transmission of hepatitis C virus (HCV) detected by HCV-RNA analysis.

The rate of transmission of hepatitis C virus (HCV) from patients with chronic hepatitis C to their children was studied. Of the 64 children with a parent with chronic hepatitis C, two (3%) had abnormal alanine aminotransferase (ALT) activities, six (9%) had anti-HCV detected by c100 ELISA, seven (11%) had anti-HCV detected by ELISA-II, and 21 (33%) had HCV-RNA by polymerase chain reaction (PCR). Anti-HCV detected by ELISA-II disappeared within six months in all six infants. Of the five children whose mothers were given a blood transfusion after the child's first birthday, none had anti-HCV or HCV-RNA. In the five families whose elder or eldest offspring had HCV-RNA, all of the younger offspring had HCV-RNA. The vertical transmission rate of HCV was low if judged by the presence of anti-HCV or abnormal ALT values, but the rate was high (33%) if judged by the presence of HCV-RNA.

Adolescent↗
PubMed1992

Frequency and distribution of phenylketonuric mutations in Orientals.

The frequency and distribution of eight mutations (R111X, IVS4nt-1, Y204C, R243Q, IVS7nt-2, W326X, Y356X, and R413P) in the phenylalanine hydroxylase gene of Orientals in Japan and Korea were examined by allele-specific oligonucleotide hybridization. The mutant alleles comprised 54 and 55% of the phenylketonuria (PKU) chromosomes examined in 36 patients in Japan and 10 patients in Korea, respectively. The spectrum of PKU mutations in Japan was similar to that in China, particularly in northern China, but different from that in Korea. The IVS4nt-1 mutation had a high frequency in Korea and southern China, due to the result of the founder effect and genetic drift. The R413P mutation, which may have originated in the regions surrounding the Baikal, expanded to northern China and Japan. We did not find Caucasian mutations in the Japanese or Korean PKU chromosomes. Thus, PKU mutations occurred after racial divergence between Caucasians and Mongoloids, and there were different founding populations for PKU in the two populations.

Alleles↗